Considering Diversified Treatment Strategies to Combat Gonorrhea Resistance

The FDA’s December 2025 dual approval of zoliflodacin (Nuzolvence) and gepotidacin (Blujepa), which were the first new gonorrhea-indicated antibiotics in decades, arrived against a backdrop of accelerating resistance.¹ World Health Organization surveillance data released the same month documented ceftriaxone susceptibility declining to approximately 5% in some regions, up from less than 1% just years prior, underscoring the fragility of the current empiric standard.²

“We are now seeing the emergence of strains of gonorrhea that harbor high level resistance to ceftriaxone and become very prevalent around the world, and so we do need a diversified regimen. There are a couple ways that this can take shape,” said Lao-Tzu Allan-Blitz, MD, MPH, assistant professor in the Division of Infectious Diseases at the David Geffen School of Medicine at UCLA. “We can introduce new antibiotics, novel therapeutics, and rapid molecular tests that predict resistance to antibiotics we used to use, and can then sort of bring them back, and we are now actually having tests for those antibiotics that are becoming increasingly available.”

Allan-Blitz spoke with Contagion at the recent ASM Microbe 2026 in Washington, DC.

Allan-Blitz says resistance-guided therapy offers one path forward. “We've been using ceftriaxone since the early 2000s…but still the majority of cases of gonorrhea are susceptible to ciprofloxacin. So, if we could rapidly predict ciprofloxacin resistance or susceptibility, we could actually use it for most cases, and we've done some genomic work to characterize the single mutation that predicts ciprofloxacin resistance.”

Molecular assays targeting the single-nucleotide polymorphism at codon 91 of the gyrA gene — a reliable predictor of ciprofloxacin susceptibility — have been implemented at select academic medical centers and through several private reference laboratories, demonstrating cure rates of 98% when the wild-type genotype is confirmed.

FDA clearance for these assays remains pending, and the absence of insurance reimbursement continues to limit broader laboratory adoption. Globally, access gaps are more acute: most gonorrhea cases worldwide are managed syndromically in settings without any diagnostic infrastructure, driving resistance through empiric overtreatment.

“The more we can tailor therapy and make it precise, the slower we will evolve to resistance,” said Allan-Blitz.

References

1.Drugs.com. FDA approves two new antibiotics, zoliflodacin and gepotidacin, to treat drug-resistant gonorrhea. December 15, 2025. https://www.drugs.com/news/fda-approves-two-new-antibiotics-zoliflodacin-gepotidacin-resistant-gonorrhea-127959.html

2.Managed Healthcare Executive. WHO warns of global rise in drug-resistant gonorrhea. Published May 2, 2026. https://www.managedhealthcareexecutive.com/view/who-warns-of-global-rise-in-drug-resistant-gonorrhea